Implant for heart valve

ABSTRACT

An implant includes a clip and a clip-controller interface. The clip is disposed laterally from a central longitudinal axis of the implant, includes first and second arms articulatably coupled to each other, and sandwiches a leaflet of a heart valve between the first and second arms by articulation between the first and second arms, such that the second arm is disposed laterally from the first arm. The clip-controller interface is reversibly coupled to a clip controller of a delivery tool, and includes first and second portions. The first portion is linearly slidable by the clip controller. The second portion is articulatably coupled to the first portion and to the second arm, such that linear sliding of the first portion causes the second portion to (i) articulate with respect to the first portion, and (ii) push the second arm to articulate toward the axis. Other embodiments are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.16/284,331 to HaCohen, filed Feb. 25, 2019, which published as US2019/0183644, and which is a Continuation of U.S. application Ser. No.15/197,069 to Gross et al., filed Jun. 29, 2016, which published as US2016/0310274 (now U.S. Pat. No. 10,226,341), and which is a Continuationof U.S. application Ser. No. 14/237,258 to Gross et al., which publishedas US 2014/0257475 (now U.S. Pat. No. 9,387,078), and which is the USNational Phase of PCT Patent Application IL2012/000293 to Gross et al.,filed Aug. 5, 2012, which published as WO 2013/021375, and which:

-   -   (1) claims priority from:        -   U.S. 61/515,372 to Gross et al., filed Aug. 5, 2011;        -   U.S. 61/525,281 to Gross et al., filed Aug. 19, 2011;        -   U.S. 61/537,276 to Gross et al., filed Sep. 21, 2011;        -   U.S. 61/555,160 to Gross et al., filed Nov. 3, 2011;        -   U.S. 61/588,892 to Gross et al., filed Jan. 20, 2012; and        -   U.S. application Ser. No. 13/412,814 to Gross et al., filed            Mar. 6, 2012, which published as US 2013/0035759 (now U.S.            Pat. No. 8,852,272), all of which are incorporated herein by            reference; and    -   (2) is a continuation-in-part of U.S. application Ser. No.        13/412,814 to Gross et al., filed Mar. 6, 2012, which published        as US 2013/0035759 (now U.S. Pat. No. 8,852,272).

This application is related to PCT application IL2012/000292 to Gross etal., entitled, “Techniques for percutaneous mitral valve replacement andsealing,” filed Aug. 5, 2012, which published as WO 2013/021374.

FIELD OF THE INVENTION

Some applications of the present invention relate in general to valvereplacement. More specifically, some applications of the presentinvention relate to prosthetic valves for replacement of a cardiacvalve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by thecombination of ischemic dysfunction of the papillary muscles, and thedilatation of the ventricle that is present in ischemic heart disease,with the subsequent displacement of the papillary muscles and thedilatation of the valve annulus.

Dilation of the annulus of the valve prevents the valve leaflets fromfully coapting when the valve is closed. Regurgitation of blood from theventricle into the atrium results in increased total stroke volume anddecreased cardiac output, and ultimate weakening of the ventriclesecondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some applications of the invention, a prosthetic valve support isprovided for facilitating minimally invasive (e.g., transcatheter and/ortransluminal) implantation of a prosthetic valve at a native valve of asubject. The native valve typically has native check valvefunctionality, i.e., it functions as a check valve. It is understoodthat a diseased valve has sub-optimal native check valve functionality,however the term “check valve functionality,” as used in the context ofthe specification and in the claims, when used with respect to a nativevalve, refers to the native level of check valve functionality of thenative valve. The prosthetic valve support is typically couplable to thenative valve (e.g., to leaflets thereof) of the subject withouteliminating the check valve functionality of the native valve. Theprosthetic valve is subsequently implanted at the native valve bycoupling the prosthetic valve to the prosthetic valve support, typicallyby expanding the prosthetic valve within one or more openings defined bythe prosthetic valve support. The implantation of the prosthetic valveat the native valve replaces, at least in part, the check valvefunctionality of the native valve with substitute check valvefunctionality of the prosthetic valve. The prosthetic valve supportcomprises tissue-engaging elements, such as clips. Typically, but notnecessarily, the prosthetic valve support further comprises (1) anupstream support portion, configured to be placed against an upstreamsurface of the native valve, and shaped to define one of the openings,and (2) a stabilizing element, shaped to define another of the openings.

For some applications, the prosthetic valve support is configured to becoupled to the native valve (e.g., to leaflets thereof) withouteliminating the check valve functionality of the native valve, byallowing (1) the native leaflets to define a single orifice, and (2) thenative valve to function as a single check valve (e.g., to function in amanner that is generally similar to the natural (e.g., physiological)function of the native valve). For some applications, the prostheticvalve support is configured to be coupled to the native valve (e.g., toleaflets thereof) without eliminating the check valve functionality bycoupling together respective portions of two leaflets, such that (1) thenative leaflets define two orifices, and (2) the native valve functionsas two (e.g., parallel) check valves.

For some applications, it is hypothesized that the use of atwo-component implant (i.e., comprising the prosthetic valve support anda separate prosthetic valve), advantageously facilitates delivery of theprosthetic valve via a catheter narrower than 28 Fr (e.g., by allowingthe use of a ‘minimalistic’ prosthetic valve, such as a prosthetic valvewith few or no appendages).

For some applications, it is hypothesized that the use of a prostheticvalve support that does not eliminate check valve functionality of thenative valve, facilitates the separate delivery of the prosthetic valvesupport and the prosthetic valve (i.e., a two-stage delivery), andthereby further facilitates the use of a narrow catheter.

For some applications, it is further hypothesized that the use of theprosthetic valve support enhances the check valve functionality of thenative valve, and thereby provides both (1) “repair” of the nativevalve, and (2) an implantation site that is pre-prepared for subsequentimplantation of a prosthetic valve at a later date, should suchimplantation be subsequently considered necessary.

There is therefore provided, in accordance with an application of thepresent invention, apparatus for use with a prosthetic valve forimplantation at a native valve of a subject, the native valve includingat least one native leaflet, the apparatus including:

a prosthetic valve support, including:

-   -   an upstream support portion, being configured to be placed        against an upstream side of the native valve, and having an        inner perimeter that defines an opening that is configured to        receive the prosthetic valve, and    -   at least one clip:        -   including at least two clip arms and a clip-controller            interface, the clip-controller interface being coupled to at            least one of the clip arms, and        -   being configured to be coupled to a native leaflet of the            native valve; and

at least one clip controller, reversibly couplable to theclip-controller interface, and configured to facilitate opening andclosing of the clip.

In an application, the at least two clip arms include a first clip arm,configured to be disposed against an upstream surface of the leaflet,and a second clip arm, configured to be disposed against a downstreamsurface of the leaflet.

In an application, the clip controller is configured to facilitateopening and closing of the clip irrespective of a state of expansion ofthe prosthetic valve support.

In an application, the at least one clip includes at least a first clipand a second clip, and the second clip is openable and closeableindependently of the first clip.

In an application, the at least one clip includes at least a first clipand a second clip, and the first clip is fixedly coupled to the secondclip, and is configured to be decoupled from the second clip.

In an application, the at least one clip is configured to be coupled toa single native leaflet of the native valve.

In an application, the at least one clip is configured to be lockablesuch that the first clip arm is locked with respect to the second cliparm.

In an application:

the native valve includes at least a first native leaflet and a secondnative leaflet,

the at least one clip includes at least a first clip and a second clip,the first clip being configured to be coupled to the first leaflet, andthe second clip being configured to be coupled to the second leaflet,and

the prosthetic valve support is configured such that, when (1) theupstream support portion is disposed against the upstream side of thenative valve, (2) the first clip is coupled to the first leaflet, and(3) the second clip is coupled to the second leaflet, the first clipmoves toward the second clip during ventricular systole of the subject,and moves away from the second clip during ventricular diastole of thesubject.

In an application, the clip is flexibly coupled to the upstream supportportion.

In an application, the clip is coupled to the upstream support portionvia a flexible connector, the flexible connector having a length fromthe upstream support portion to the clip, and the length of the flexibleconnector is variable.

In an application, the upstream support portion is generally flat.

In an application, the inner perimeter defines the opening, such thatthe opening has a depth and a width, and the width of the opening ismore than four times greater than the depth of the opening.

In an application, the upstream support portion has a free inner edge,and the free inner edge defines the inner perimeter.

In an application, the inner perimeter defines an opening that has adiameter, and the upstream support portion has a diameter that is atleast 10 percent greater than the diameter of the opening.

In an application, no part of the prosthetic valve support thatcircumscribes a space that has a perimeter greater than 60 mm has aheight of more than 20 mm.

There is further provided, in accordance with an application of thepresent invention, apparatus for facilitating implantation of aprosthetic valve at a native heart valve of a subject, the native heartvalve including a native annulus and a plurality of native leaflets thatprovide check valve functionality, the apparatus including a prostheticvalve support, the prosthetic valve support:

being configured to be transluminally-delivered to the native valve andto be deployed at the native valve, and

including one or more tissue-engaging elements, configured to couple theprosthetic valve support to the native leaflets without eliminating thecheck valve functionality.

In an application, the tissue-engaging elements are configured to couplethe prosthetic valve support to the native leaflets without eliminatingthe check valve functionality, by coupling the prosthetic valve supportto the native leaflets such that:

the native leaflets define a single orifice therebetween, and

the native valve functions as a single check valve.

In an application, the tissue-engaging elements include at least a firsttissue-engaging element and a second tissue-engaging element, and thefirst tissue-engaging element is transluminally controllableindependently of the second tissue-engaging element.

In an application, the tissue-engaging elements are configured to couplethe prosthetic valve support to the native leaflets without eliminatingthe check valve functionality, by coupling the prosthetic valve supportto the native leaflets such that:

the native leaflets define two orifices therebetween, and

the native valve functions as two check valves.

In an application:

the native leaflets include a first leaflet and a second leaflet,

the tissue-engaging elements include at least a first tissue-engagingelement and a second tissue-engaging element,

the first tissue-engaging element is configured to be coupled to aportion of the first leaflet, and

the second tissue-engaging element is configured to be coupled to aportion of the second leaflet and to the first tissue-engaging element.

In an application, the apparatus is configured such that the firsttissue-engaging element is transluminally, intracorporeally decouplablefrom the second tissue-engaging element.

In an application, the prosthetic valve support includes an annularupstream support portion:

shaped to define an opening therethrough,

coupled to the tissue-engaging elements,

configured to be placed against an upstream surface of the nativeannulus, and

configured to be transluminally, intracorporeally, coupled to theprosthetic valve.

In an application, the apparatus further includes the prosthetic valve,and the prosthetic valve includes a flexible netting at at least anupstream portion of the prosthetic valve, and the netting is configuredto facilitate coupling of the prosthetic valve to the upstream supportportion.

In an application, the prosthetic valve support includes one or moreflexible connectors, and each tissue-engaging element is flexiblycoupled to the upstream support portion by a respective flexibleconnector.

In an application, each flexible connector has a length, and isconfigured such that the length is variable while the tissue-engagingelements are coupled to the native leaflets.

In an application, the upstream support portion has a compressedconfiguration and an expanded configuration, and is configured (1) to bedelivered to the native valve in the compressed configuration, and (2)to be expanded into the expanded configuration at the native valve.

In an application, the apparatus further includes one or more couplingleads, and the apparatus is configured such that the expansion of theupstream support portion is controllable using the coupling leads.

In an application, each coupling lead passes around at least a portionof the upstream support portion, and the apparatus is configured suchthat the upstream support portion is recompressible from the expandedconfiguration toward the compressed configuration, by pulling on thecoupling leads.

In an application, the prosthetic valve support includes a downstreamstabilizing element:

shaped to define an opening therethrough,

coupled to the tissue-engaging elements,

configured to be placed entirely downstream of the native annulus, and

configured to be coupled to the prosthetic valve.

In an application, the apparatus further includes the prosthetic valve,and the prosthetic valve includes a valve body and one or morevalve-anchoring elements, the valve-anchoring elements being configuredto sandwich the downstream stabilizing element between thevalve-anchoring elements and the valve body.

In an application, the prosthetic valve support is configured to becoupled to the native leaflets such that no portion of the prostheticvalve support is disposed upstream of the native annulus.

In an application, the tissue-engaging elements include clips, each clipincluding a plurality of clip arms, including at least a first clip armand a second clip arm, and configured to couple at least a portion ofone of the native leaflets between the first and second clip arms.

In an application, the apparatus further includes a clip controller,configured to be advanced transluminally to the native valve, and eachclip includes a clip-controller interface, configured to be reversiblycoupled to the clip controller, and to facilitate extracorporeal controlof the clips independently of deployment of the prosthetic valvesupport.

In an application, each clip is configured such that movement of atleast a portion of the clip-controller interface by a first distance,changes a distance between a portion of the first clip arm and a portionof the second clip arm by a second distance that is more than 1.5 timesgreater than the first distance.

In an application, the tissue-engaging elements are configured tosuturelessly couple the prosthetic valve support to the native leaflets.

In an application, the prosthetic valve support is configured to betransluminally, intracorporeally, couplable to the prosthetic valve.

There is further provided, in accordance with an application of thepresent invention, a method for use at a native valve of a subject, thenative valve including at least one native leaflet that provides nativecheck valve functionality, the method including:

transluminally delivering a prosthetic valve support to the nativevalve;

coupling a prosthetic valve support to the leaflet of the native valvewithout eliminating the native check valve functionality; and

subsequently, replacing, at least in part, the native check valvefunctionality with a substitute check valve functionality, by coupling aprosthetic valve to the prosthetic valve support.

In an application:

the prosthetic valve support includes at least one clip,

the clip includes two or more clip arms and a clip-controller interface,and

coupling the prosthetic valve support to the leaflet includes changingan angular disposition between the clip arms by moving theclip-controller interface.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native heart valve of asubject, the apparatus including:

a first expandable prosthetic valve component, including a crimpableframe, and configured to be transcatheterally advanceable toward thenative valve while the first prosthetic valve component is in a crimpedstate thereof;

a second expandable prosthetic valve component, including a crimpableframe, and configured to be transcatheterally advanceable toward thenative valve, placeable in the native valve while the second prostheticvalve component is in a crimped state thereof, and couplable to thefirst prosthetic valve component, expansion of the second prostheticvalve component facilitating coupling of the second prosthetic valvecomponent to the first prosthetic valve component; and

one or more tissue-engagement elements, coupled to at least one of theprosthetic valve components, the tissue-engagement elements configured,when the prosthetic valve component is in an expanded state thereof, toextend from the prosthetic valve component, and to inhibit a proximalmovement of the prosthetic valve component.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a prosthetic valve forimplantation at a native valve of a subject, the native valve (1)defining an orifice, (2) including at least one native leaflet, having anative beating, and (3) having a native blood flow regulationfunctionality, the apparatus including:

-   -   a prosthetic valve support, including:    -   an upstream support portion, configured to be placed against an        upstream side of the native valve, to have an inner perimeter        that defines an opening that is configured to receive the        prosthetic valve, and        -   at least one clip, configured to be coupled to a native            leaflet of the native valve, the clip including a plurality            of clip arms, at least one clip arm coupled to a            clip-controller interface; and    -   a clip controller, couplable to the clip-controller interface,        and configured to control a relative angular disposition between        the clip arms.

For some applications, techniques described herein are practiced incombination with techniques described in one or more of the referencescited in the Background section and Cross-references section of thepresent patent application.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-D are schematic illustrations of apparatus, comprising aprosthetic valve support, for facilitating implantation of a prostheticheart valve at a native heart valve of a subject, in accordance withsome applications of the invention;

FIGS. 2A-D are schematic illustrations of the prosthetic valve support,and components thereof, in accordance with respective applications ofthe invention;

FIGS. 3A-I are schematic illustrations of steps in the delivery andimplantation of the prosthetic valve support at the native heart valveof the subject, and the use thereof to facilitate implantation of theprosthetic valve, in accordance with some applications of the invention;

FIGS. 4A-F are schematic illustrations of a system for facilitatingcontrolled expansion and/or retrievability of an upstream supportportion of the prosthetic valve support, in accordance with someapplications of the invention;

FIG. 5 is a schematic illustration of a step in the implantation of theprosthetic valve support, in accordance with some applications of theinvention;

FIGS. 6A-B are schematic illustrations of a prosthetic valve supportcomprising tissue-engaging elements that are couplable to each other,and decouplable from each other, in accordance with some applications ofthe invention;

FIG. 7 is a schematic illustration of a prosthetic valve supportcomprising the upstream support portion and three clips, in accordancewith some applications of the invention;

FIG. 8 is a schematic illustration of a step in the implantation of theprosthetic valve, facilitated by the prosthetic valve support, inaccordance with some applications of the invention; and

FIGS. 9A-C are schematic illustrations of the prosthetic valve supportcomprising variable-length connectors, in accordance with respectiveapplications of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-D, which are schematic illustrations ofapparatus 20, comprising a prosthetic valve support 22 for facilitatingimplantation of a prosthetic heart valve at a native heart valve of asubject, in accordance with some applications of the invention.Prosthetic valve support 22 comprises one or more tissue-engagingelements 24 (e.g., support-anchoring elements), and is typicallyconfigured to be coupled to the native heart valve (e.g., to leafletsthereof) without eliminating check valve functionality of the nativeheart valve (described in more detail hereinbelow). Typically,prosthetic valve support 22 is configured to be transluminally,intracorporeally coupled to the native heart valve.

Typically, each tissue-engaging element 24 comprises a clip 30, whichtypically comprises a plurality of clip arms 32 (e.g., two clips arms,e.g., a first clip arm 32 a and a second clip arm 32 b), the clip beingconfigured to be coupled to a leaflet of the native valve. Clip arms 32a and 32 b are movable with respect to each other, thereby opening andclosing clip 30 (e.g., moving clip 30 between an open state and a closedstate thereof), e.g., as shown in FIG. 1B. Clip arms 32 a and 32 b aretypically articulatably coupled to each other at an articulation point31 (e.g., a coupling point), such that opening and closing clip 30comprises changing a relative angular disposition between the clip arms.Typically, each clip arm 32 has a length from a first end thereof, atwhich the clip arms are coupled to each other (e.g., at articulationpoint 31), to a second end thereof, of greater than 1.5 mm and/or lessthan 20 mm (e.g., between 3 and 10 mm). For some applications, a lengthd7 of clip arm 32 a is generally the same as a length d8 of clip arm 32b (e.g., as shown in FIG. 1B). For some applications, length d8 of cliparm 32 b is shorter than length d7 of clip arm 32 a (e.g., at least 30%shorter, such as at least 50% shorter), e.g., so as to reduce forceapplied to the leaflet of the native valve by clip arm 32 b (such as bythe second end of the clip arm).

For some applications of the invention, at least one of the clip arms(e.g., clip arm 32 b) comprises a tissue-engaging portion 48 that isarticulatably coupled to another portion of the clip arm at anarticulation point 47, such that, at a given relative angulardisposition of clip arms 32 a and 32 b (e.g., a degree of openness ofclip 30), a relative angular disposition of portion 48 with respect toclip arm 32 a, may change (e.g., may be changed). For example, for atleast some states of clip 30, the relative angular disposition of cliparm 32 a and portion 48 may be generally independent of the relativeangular disposition of clip arm 32 a and the other portion of clip arm32 b. For example, portion 48 may remain parallel with clip arm 32 a,irrespective of the angular disposition of clip arms 32 a and 32 b. Itis hypothesized that this configuration facilitates coupling of clip 30to the leaflet of the native valve, by allowing the clip to maintaincontact with both sides of the leaflet, irrespective of dimensions(e.g., thicknesses) of the leaflet to which clip 30 is coupled.

Prosthetic valve support 22 is typically configured to be implantedusing minimally-invasive procedures (e.g., percutaneously). Furthertypically, the prosthetic valve support is configured to be deliveredtransluminally (e.g., transfemorally). Alternatively, the prostheticvalve support may be configured to be delivered transthoracically (e.g.,transapically). Typically, the prosthetic valve support is configured inthis way by being compressible (e.g., crimpable) into a deliveryconfiguration, and by being configured to expand (e.g., automatically)upon deployment at the native valve. Typically, tissue-engaging elements24 (e.g., clips 30) are coupled to the leaflets of the native valvebefore prosthetic valve support 22 is fully deployed, such as while atleast part of the prosthetic valve support remains within a deliverytube (e.g., as shown in FIGS. 3B-C).

Clips 30 are typically configured to be controllable (i.e., openable andclosable) independently of each other, and/or independently ofdeployment of prosthetic valve support 22 (e.g., irrespective of a stateof deployment of the prosthetic valve support, such as irrespective of astate of expansion of an upstream support portion 60 of the prostheticvalve support, described hereinbelow).

Clip 30 typically further comprises a clip-controller interface 34,which is configured to facilitate control (e.g., opening and closing) ofthe clip from outside the subject (i.e., to facilitate extracorporealcontrol of the clip), e.g., by a physician. Clip-controller interface 34is reversibly couplable to a clip controller 36, which is itselfextracorporeally controllable, e.g., by extending from outside thesubject to the clip-controller interface. Clip 30 is thereby typicallytransluminally controllable. Typically, clip controller 36 facilitatescontrol of the clip by applying a force to clip-controller interface 34,e.g., by transferring an extracorporeally-applied force to theclip-controller interface. Typically, clip controller 36 is integralwith delivery apparatus that is used to deliver support 22 to the nativevalve (e.g., delivery apparatus 140, described hereinbelow withreference to FIGS. 3A-D).

Clip-controller interface 34 is typically articulatably coupled to atleast clip arm 32 b (e.g., at an articulation point 35), and/orcomprises one or more articulatably coupled portions (e.g., a firstinterface portion 34 a and a second interface portion 34 b). Clips 30are typically configured such that movement of clip-controller interface34 by a first distance dl, moves clip arm 32 b by a second distance d2that is typically more than 1.5 times (e.g., more than 2 times, such asmore than 4 times) greater than distance d1. That is, a relatively largerange of movement of clip arm 32 b is provided by a relatively smallrange of movement of clip-controller interface 34, e.g., clip-controllerinterface 34, clip arm 32 b, and/or the coupling therebetween, acts as alever. Clip 30 is typically configured such that clip arm 32 b canarticulate over more than 60 degrees, e.g., more than 100 degrees, suchas up to 180 degrees, around articulation point 31, with respect to cliparm 32 a.

It is hypothesized that, for some applications, angles of articulationgreater than 80 degrees (e.g., greater than 120 degrees, such as up to180 degrees) facilitate (1) repeated coupling to, and decoupling from,the native leaflets (e.g., multiple attempts to couple to the nativeleaflets), and (2) retrieval of the clips and/or the entire prostheticvalve support (e.g., into a delivery tube).

Clip-controller interface 34 (e.g., portion 34 a thereof) is typicallyslidably coupled to at least clip arm 32 a. That is, moving ofclip-controller interface 34 typically includes sliding of theclip-controller interface with respect to clip arm 32 a (e.g., by usingclip controller 36).

For some applications of the invention, at least one of clip arms 32comprises or defines grips 38 and/or teeth 40, which are configured tofacilitate coupling of clip 30 to a native leaflet of the native valve.Typically, grips 38 are configured to atraumatically grip the leafletand teeth 40 are configured to grip, fold around, and/or pierce theleaflet. For some applications of the invention, at least a portion ofclip arms 32 is covered with a padding (not shown), configured tocushion the contact between the clip arms and the leaflet.

Typically, clip 30 is lockable, such that clip arm 32 b is locked (e.g.,immobile) with respect to clip arm 32 a. FIGS. 1B-D show clip 30comprising a locking element 50 (e.g., a securing element), whichfacilitates locking of the clip. Locking element 50 typically comprisesat least one ratchet mechanism 52, comprising (1) a rack 51, comprisinga plurality of sockets 54, and (2) an engaging element 56 (e.g., a pawl,or a tooth). Typically, rack 51 is defined by, or is fixedly coupled to,clip arm 32 a, and engaging element 56 is coupled to, or defined by,clip-controller interface 34. However, the scope of the inventionincludes other (e.g., inverse) arrangements of ratchet mechanism 52.

FIG. 1B shows clip 30 in an unlocked configuration thereof, in which anobstructing element 58 (e.g., a restraint) is disposed between rack 51and engaging element 56, thereby inhibiting (e.g., obstructing) engagingelement 56 from engaging rack 51, and thereby facilitating the openingand closing of the clip (i.e., movement between open and closed statesthereof). Typically, obstructing element 58 is integral with deliveryapparatus that is used to deliver support 22 to the native valve (e.g.,delivery apparatus 140, described hereinbelow with reference to FIGS.3A-D). FIG. 1B shows a front view and a back view of clip 30 in the openstate thereof, and a front view and a back view of the clip in theclosed state thereof.

FIG. 1C shows a back view of clip 30 in a locked configuration thereof,in which obstructing element 58 has been removed from between rack 51and engaging element 56 (e.g., by withdrawing the obstructing elementproximally), and an engaging element 56 has engaged the rack. Typically,element 56 is configured (e.g., shape-set) to automatically engage rack51 upon removal of obstructing element 58.

For some applications, and as shown in FIGS. 1B-D, obstructing element58 comprises a longitudinal member, such as a strip or rod, and isremoved by being withdrawn proximally. However, obstructing element 58may have other shapes and/or shape-memory features that facilitate theobstruction of engaging element 56 and/or the removal of the obstructingelement. For example, obstructing element 58 may have a generallycircular, rectangular, triangular, or hexagonal cross-section, and/ormay be shape-set to facilitate removal thereof, and thereby tofacilitate locking of the clip.

For some applications of the invention, and as shown in FIGS. 1B-D,locking element 50 comprises two ratchet mechanisms 52. The two ratchetmechanisms are offset with respect to the other, such that at a positionof clip-controller interface 34 in which the engaging element 56 of oneratchet mechanism is fully disposed in a socket 54, the engaging elementof the other ratchet mechanism is not fully disposed in a socket of theother rack (FIGS. 1C-D). This configuration increases (e.g., doubles)the number of positions within a given range in which clip-controllerinterface 34 is lockable, without reducing the size of each socket 54.That is, this configuration increases the “resolution” or “density” oflocking positions of clip 30. It is hypothesized that, for someapplications, it is advantageous to combine this configuration oflocking element 50 with the lever-like clip-controller interfacedescribed hereinabove, such that the relatively large movement of cliparm 32 b is at least partly offset by the “high resolution” of thelocking element, thereby increasing the degree of control that thephysician has on the clip.

As described hereinabove, clip-controller interface 34 is typicallyreversibly couplable to clip controller 36. Typically, this reversiblecoupling is facilitated by a projection 42, defined by clip controller36, which is configured to be disposed within, and removed from, adepression 44, defined by clip-controller interface 34. Furthertypically, projection 42 is configured (e.g., shape-set) to move outfrom depression 44, and is prevented from moving out of depression 44 byobstructing element 58. Following the locking of clip 30 by withdrawingobstructing element 58 (FIG. 1C), the obstructing element is furtherwithdrawn (FIG. 1D), thereby releasing projection 42 from depression 44,and thereby decoupling clip controller 36 from clip-controller interface34. Clip 30 is typically configured such that the physician mayrepeatedly lock and unlock clip 30 (e.g., by partially withdrawing andreplacing obstructing element 58) before finally decoupling thecontroller (e.g., by completely withdrawing obstructing element 58),such as after confirming that clip 30 has been successfully coupled tothe native leaflet.

As described hereinabove, clips 30 are typically configured to becontrollable (i.e., openable and closable) independently of each other,and/or independently of deployment of prosthetic valve support 22. Clips30 are further typically lockable and/or decouplable from controller 36independently of each other, and/or independently of deployment of theprosthetic valve support. It is to be noted that clips 30 are configuredto couple the prosthetic valve support to the native leafletssuturelessly.

Referring again to FIG. 1A, prosthetic valve support 22 typicallycomprises a generally annular upstream support portion 60 (e.g., anannular portion), shaped to define an opening 61 (e.g., an aperture)therethrough, and to be placed against an upstream side of the nativevalve. Typically, upstream support portion 60 comprises an expandablelattice-structure frame 62 (e.g., comprising a plurality of struts),covered by a covering 64. Opening 61 is defined by an inner perimeter 68of the prosthetic valve support. For some applications, frame 62 definesa plurality of barbs 67 that protrude radially inwardly from innerperimeter 68, and facilitate coupling of a prosthetic valve to theprosthetic valve support (e.g., as described hereinbelow with referenceto FIGS. 3H-I).

Upstream support portion 60 typically has shape-memory (e.g., resilient,pseudoelastic and/or superelastic) properties. Typically, frame 62comprises a shape-memory (e.g., resilient, pseudoelastic and/orsuperelastic) material, such that upstream support portion 60 iscompressible (e.g., crimpable) when a compressive force is applied(e.g., prior to implantation), and re-expandable when the compressiveforce is removed (e.g., during implantation). Non-limiting examples ofmaterials that frame 62 may comprise, include nickel-titanium (nitinol),stainless steel, nickel cobalt, cobalt chrome, titanium, tantalum, andpalladium.

Non-limiting examples of materials that covering 64 may comprise,include polyethylene terephthalate (e.g., polyester),polytetrafluoroethylene (e.g., Teflon, ePTFE), and pericardial tissue.For some applications, covering 64 comprises a fabric. Typically, athickness of the covering is less than 0.5 mm, such as less than 0.2 mm,e.g., less than 0.1 mm, or less than 0.05 mm.

FIG. 1A shows upstream support portion 60 in an expanded (e.g., fullyuncompressed and/or deployed) configuration thereof, in which upstreamsupport portion 60 (i.e., an outer perimeter 69 thereof) typically has adiameter d3 that is greater than 40 mm and/or less than 80 mm (e.g.,40-80 mm, such as 40-70 mm, such as 40-60 mm). That is, an outerdiameter of upstream support portion 60 is typically greater than 40 mmand/or less than 80 mm (e.g., 40-80 mm, such as 40-70 mm, such as 40-60mm). Opening 61, defined by inner perimeter 68, typically has a diameterd4 of greater than 20 mm and/or less than 35 mm (e.g., 20-35 mm, such as23-32 mm, such as 25-30 mm). That is, an inner diameter of upstreamsupport portion 60 is typically greater than 20 mm and/or less than 35mm (e.g., 20-35 mm, such as 23-32 mm, such as 25-30 mm). Typically,diameter d3 is at least 10% (e.g., at least 50%, such as at least 80%)greater than diameter d4.

Upstream support portion 60 is typically compressible (e.g., crimpable;for delivery to the native valve) into a generally cylindrical shape inwhich inner perimeter 68 defines a downstream end 71 of the cylindricalshape, and outer perimeter 69 defines an upstream end 73 of thecylindrical shape (see FIG. 3A). Typically, the generally cylindricalshape of upstream support portion 60 has a transverse cross-sectionaldiameter (e.g., a width) of greater than 3 mm and/or less than 9 mm(e.g., 3-9 mm, such as 5-8 mm, such as 6-7 mm), and a height, from theupstream end to the downstream end, of greater than 11 mm and/or lessthan 30 mm (e.g., 11-30 mm, such as 15-30 mm, such as 15-25 mm).

In the expanded configuration thereof, upstream support portion 60 istypically (but not necessarily) generally flat (e.g., laminar, and/orplanar). For some applications, in the expanded configuration, upstreamsupport portion 60 assumes a frustoconical shape. Upstream supportportion 60 typically has a thickness of less than 5 mm, e.g., less than2 mm, such as between 0.3 mm and 2 mm. Inner perimeter 68 (and therebyopening 61) thereby typically has a depth d10 (e.g., a height) from anupstream side 59 of the upstream support portion to a downstream side 63of the upstream support portion. Depth d10 is less than 5 mm, e.g., lessthan 2 mm, such as between 0.3 mm and 2 mm. Typically, diameter d4 ofopening 61 is more than 4 times (e.g., more than 6 times, such as morethan 10 times) greater than depth d10. That is, opening 61 is more than4 times (e.g., more than 6 times, such as more than 10 times) wider thanit is deep. Typically, in the expanded configuration, upstream supportportion 60 has a total height of less than 10 mm (e.g., less than 5 mm,such as less than 2 mm).

Typically, inner perimeter 68 comprises, or is defined by, a free inneredge of upstream support portion 60. That is, opening 61 resembles ahole cut out of a lamina (e.g., out of a disc). For some applications,inner perimeter 68 comprises, or is defined by, a curved and/or foldedinner edge of upstream support portion 60. If the inner perimeter ofupstream support portion 60 comprises, or is defined by, a curved orfolded edge, then a radius of curvature of the curved or folded edge istypically less than 2.5 mm, such as less than 1 mm. That is, the curveor fold of the edge is generally sharp, such that when viewed fromwithin opening 61, the curved or folded edge looks generally like a freeedge.

Prosthetic valve support 22 typically comprises two or moretissue-engaging elements 24 (e.g., clips 30), coupled to inner perimeter68 of upstream support portion 60. For such applications, the twotissue-engaging elements are typically disposed opposite each other(e.g., at 180 degrees around inner perimeter 68 from each other).

Typically, tissue-engaging elements 24 (e.g., clips 30) are coupled toupstream support portion 60 (e.g., inner perimeter 68 thereof) by aflexible connector 70, which may comprise polyethylene terephthalate(e.g., polyester), polytetrafluoroethylene (e.g., Teflon, ePTFE), afabric, nitinol, and/or any other suitable material. Thereby,tissue-engaging elements 24 (e.g., clips 30) are typically flexiblycoupled to upstream support portion 60, and/or are able to moveindependently of each other. Connector 70 may be coupled to upstreamsupport portion 60 and tissue-engaging elements 24 using sutures,welding, and/or any other suitable technique known in the art.

Prosthetic valve support 22 typically further comprises a stabilizingelement 80, coupled to clips 30 (e.g., to a downstream portion thereof).Typically, stabilizing element 80 forms a ring shape that defines anopening 81 (e.g., an aperture), and is typically inelastic and at leastpartly flexible. Opening 81 typically, but not necessarily, has adiameter that is generally equal to diameter d4 of opening 61.Non-limiting examples of materials that stabilizing element 80 maycomprise include polyethylene terephthalate (e.g., polyester), PTFE(e.g., ePTFE), nylon, cotton, nitinol, stainless steel, nickel cobalt,cobalt chrome, titanium, tantalum and palladium. Typically, and as shownin FIG. 1A, stabilizing element 80 comprises (1) an outer coat 82 of aflexible material (e.g., polyester), which typically providesinelasticity, and (2) an inner strip 84 of a shape-memory material(e.g., nitinol), which is typically configured (e.g., shape-set) to biaselement 80 to assume a ring-shaped configuration.

Stabilizing element 80 (and thereby opening 81) typically has a depthd11 (e.g., a height from a most upstream part to a most downstream part)of less than 20 mm (e.g., less than 10 mm, e.g., less than 5 mm, such asless than 1 mm). As described hereinabove, inner perimeter 68 ofupstream support portion has a depth d10 of less than 5 mm. Typically,in the expanded configuration, no part of prosthetic valve support 22that circumscribes a space that has a perimeter greater than 60 mm(e.g., as upstream support portion 60 and stabilizing element 80typically do) has a height of more than 20 mm. For some applications, inthe expanded configuration, no part of the support that circumscribes aspace that has a perimeter greater than 60 mm has a height of more than10 mm. For some applications, in the expanded configuration, no part ofthe support that circumscribes a space that has a perimeter greater than60 mm has a height of more than 5 mm.

Reference is made to FIGS. 2A-D, which are schematic illustrations ofprosthetic valve support 22 and/or components thereof, in accordancewith respective applications of the invention. As described hereinabove,upstream support portion 60 is generally annular. For some applications,and as shown in FIG. 1A, upstream support portion 60 has a generallycircular outer perimeter 69. FIG. 2A shows an alternative embodiment inwhich upstream support portion 60 comprises an upstream support portion90, which has a non-circular outer perimeter 99. FIG. 2A shows outerperimeter 99 as generally oval, with a “squashed” portion 92. Such aconfiguration may, for example, facilitate placement of upstream supportportion 90 at a mitral valve of the subject, with squashed portion 92facing the interatrial septum. It is to be noted, that the scope of theinvention includes upstream support portions having other shapes,configured according to the anatomical site at which they are to beplaced. For example, for some applications, upstream support portion 60and/or upstream support portion 90 may have radially-protruding bulgesor wings (not shown), configured to stabilize the upstream supportportion and/or to inhibit leakage between the native valve and theupstream support portion.

As described hereinabove, upstream support portion 60 typicallycomprises an expandable lattice-structure frame 62. FIG. 2B shows analternative embodiment in which upstream support portion 60 comprises abraided upstream support portion 100, which comprises a braidedstructure of intertwining strands 102, at least some of which areslidable past (e.g., over, under) each other. Typically, strands 102comprise a shape-memory material such as, but not limited to, nitinol.Upstream support portion 100 is transluminally deliverable in acompressed configuration, and is expandable to an annular, expandedconfiguration at the native valve. Typically, support 100 is configuredto automatically expand to the expanded configuration, and thisexpansion is controlled by progressively releasing (e.g., looseningand/or unthreading) a restricting element 104 (e.g., a drawstring),which, when threaded through parts of upstream support portion 100(e.g., one or more rings 106 thereof), is configured to restrictexpansion of the upstream support portion (e.g., to retain the upstreamsupport portion in the compressed configuration thereof). FIG. 2B showssequential stages in the deployment of upstream support portion 100 froma delivery tube 108. Typically, upstream support portion 100 isrecompressible by tightening (e.g., pulling) the restricting element.

As described hereinabove, prosthetic valve support 22 comprises one ormore tissue-engaging elements 24, and typically further comprisesupstream support portion 60 and/or stabilizing element 80. FIG. 1A showsprosthetic valve support 22 comprising both upstream support portion 60and stabilizing element 80. FIG. 2C shows an alternative embodiment inwhich prosthetic valve support 22 comprises a prosthetic valve support322, which does not comprise stabilizing element 80. FIG. 2D shows analternative embodiment in which prosthetic valve support 22 comprises aprosthetic valve support 422, which does not comprise an upstreamsupport portion (e.g., upstream support portion 60). For someapplications of the invention, when implanted at the native valve, noportion of prosthetic valve support 422 is disposed upstream of thenative annulus.

It is to be noted that upstream support portions 90 and 100, andprosthetic valve supports 322 and 422, may be used (e.g., combined) withapparatus and methods described elsewhere herein. For example, theupstream support portion of any of the prosthetic valve supportsdescribed herein may be replaced with upstream support portion 90 orupstream support portion 100, resulting in alternative prosthetic valvesupports. Furthermore, these resulting prosthetic valve supports, aswell as prosthetic valve supports 322 and 422, may be used incombination with other techniques described herein (e.g., with referenceto FIGS. 3A-I, 4A-F, 5, 6A-B, 7, 8, and/or 9A-C), mutatis mutandis.

Reference is made to FIGS. 3A-I, which are schematic illustrations ofsteps in the delivery and implantation of prosthetic valve support 22 ata native heart valve 120 of heart 250 of a subject, and the use thereofto facilitate implantation of a prosthetic valve 150, in accordance withsome applications of the invention. FIGS. 3A-I show native valve 120 ascomprising a mitral valve 122 of the subject, but it is to be noted thatthe scope of the invention includes the use of prosthetic valve support22 at other heart valves of the subject.

Mitral valve 122 is disposed between a left atrium 124 and a leftventricle 126 of the subject, and comprises two leaflets 128. Atrium 124is upstream of mitral valve 122 and ventricle 126 is downstream of themitral valve. Prosthetic valve support 22, in a compressed configurationthereof, is advanced transluminally (e.g., transfemorally and/ortransseptally) within a delivery tube 130 of delivery apparatus 140, toatrium 124, and between leaflets 128 (FIG. 3A).

Prosthetic valve support 22 is advanced out of delivery tube 130 and/orthe delivery tube is withdrawn from the prosthetic valve support (FIG.3B). Clips 30 (and/or other tissue-engaging elements) are typicallydisposed at a downstream portion of prosthetic valve support 22 (e.g.,downstream of downstream end 71 of upstream support portion 60) in thecompressed configuration thereof, and are thereby exposed from deliverytube 130. Stabilizing element 80 is also typically exposed from thedelivery tube, and typically forms a generally lemniscate (e.g.,figure-8) shape, defining two “loops” 83. Typically, the axis betweenloops 83 of the lemniscate is generally orthogonal to the axis betweenclips 30, and may be used to orient prosthetic valve support 22, e.g.,such that clips 30 point toward leaflets 128 of the native valve. Forexample, loops 83 may be disposed between chordae tendineae 72 of oneleaflet and those of the other leaflet, and physical contact between thechordae tendineae and the loops automatically and/or via tactilefeedback to the physician, facilitates orientation of the prostheticvalve support. Alternatively or additionally, the lemniscate shape ofstabilizing element 80 may be visualized using imaging techniques suchas fluoroscopy and/or ultrasound. Clips 30 are opened (e.g., asdescribed hereinabove with reference to FIG. 1B).

Prosthetic valve support 22 is moved upstream (e.g., proximally) so asto envelope leaflets 128 between clip arms 32 of each clip 30, and eachclip is closed around a leaflet, thereby coupling each clip to aleaflet, e.g., by clamping the leaflet between the clip arms (FIG. 3C).Each clip 30 couples to a single leaflet 128, such that one clip arm ofeach clip (e.g., clip arm 32 a) engages an upstream surface of theleaflet (e.g., an upstream side of the leaflet), and the other clip armof each clip (e.g., clip arm 32 b) engages a downstream surface of theleaflet (e.g., a downstream side of the leaflet). Although each cliptypically couples to only one leaflet, for some applications, more thanone clip couples to each leaflet.

As described hereinabove, clips 30 (and/or other tissue-engagingelements 24) are typically coupled to the leaflets of the native valvebefore prosthetic valve support 22 is fully deployed. Clips 30 aretypically locked (e.g., as described with reference to FIG. 1C), andsubsequently decoupled from clip controller 36 (e.g., as described withreference to FIG. 1D). FIGS. 3C-F show stages in the deployment ofprosthetic valve support 22 (e.g., of upstream support portion 60thereof). Upstream support portion 60 typically progressively expands asit is exposed from delivery tube 130. Thereby, typically, (1) downstreamend 71 of the cylindrical shape of the upstream support portion in thecompressed configuration thereof, expands to become inner perimeter 68of the upstream support portion in the expanded configuration thereof,and (2) subsequently, upstream end 73 of the cylindrical shape expandsto become outer perimeter 69 of the upstream support portion.

Delivery apparatus 140 typically comprises a pushing member 132.Typically, prosthetic valve support 22 (e.g., upstream support portion60 thereof) is reversibly coupled to pushing member 132, and is exposedfrom delivery tube 130 by being pushed using the pushing member.Upstream support portion 60 is typically configured (e.g., shape-set) toautomatically expand toward its expanded configuration upon beingdeployed from delivery tube 130. For some applications of the invention,the upstream support portion “pops” open from the configuration shown inFIG. 3C to the configuration shown in FIG. 3F, immediately upon exposureof upstream end 73 of the upstream support portion from delivery tube130.

For some applications, and as shown in FIGS. 3C-F, one or more holdingmembers 134, coupled to, and decouplable from, upstream support portion60, facilitate controlled expansion of the upstream support portion. Forexample, holding members 134 may be configured to allow a physician (1)to expand some portions of the upstream support portion before otherportions and/or (2) to adjust the positioning of the upstream supportportion on the upstream surface of the native valve following expansionof the upstream support portion. For some applications, two holdingmembers 134 are used, and are coupled to opposite sides of upstreamsupport portion 60 to each other (e.g., 180 degrees around the upstreamsupport portion from each other).

For some applications, and as shown in FIGS. 3D-F, three holding members134 are used. For such applications, each holding member 134 is coupledat between 90 and 180 degrees (e.g., between 100 and 150 degrees, suchas at 120 degrees) around the upstream support portion from the otherholding members. For some such applications, and as shown in FIG. 3F,the holding members are coupled to the upstream support portion suchthat, when the upstream support portion is positioned at the nativevalve, two holding members are disposed generally above respectivecommissures of the native valve, and the third holding member isdisposed generally midway around posterior leaflet 128 p of the nativevalve.

For some applications, holding members 134 comprise locking elementsand/or coupling leads (e.g., coupling wires, e.g., looped aroundrespective portions of the upstream support portion; not shown in FIGS.3D-F) that couple the holding members to the upstream support portion,and the holding members are decoupled from the upstream support portionby unlocking the locking elements and/or unlooping the loops. For someapplications of the invention, holding members 134 also facilitateretrieval of the upstream support portion, and thereby of prostheticvalve support 22, e.g., as described with reference to FIGS. 4A-F.

FIG. 3G shows prosthetic valve support 22 following coupling, deploymentand expansion (i.e., implantation) thereof at mitral valve 122, andwithdrawal of delivery apparatus 140. As described hereinabove,prosthetic valve support 22 is configured to be coupled to the nativeheart valve (e.g., to leaflets thereof) without eliminating check valvefunctionality of the native heart valve. Typically, and as shown in FIG.3G, clips 30 couple the prosthetic valve support to leaflets 128 suchthat (1) the leaflets define a single orifice, and (2) the native valvefunctions as a single check valve (e.g., functions in a manner that isgenerally similar to the natural (e.g., physiological) function of thenative valve). Stabilizing element 80 is also configured to allow suchmovement of leaflets 128, e.g., the stabilizing element is sufficientlyflexible to flex in response to the leaflets moving in response topumping of the heart. FIG. 3G shows (1) in solid, mitral valve 122(e.g., leaflets 128) closed, and the respective state of prostheticvalve support 22, and (2) in phantom, the mitral valve (e.g., theleaflets) open, and the respective state of the prosthetic valvesupport.

Thereby, when prosthetic valve support 22 is implanted at anatrioventricular valve of the subject (e.g., mitral valve 122 or atricuspid valve), clips 30 typically move away from each other duringventricular diastole, and toward each other during ventricular systole.For applications in which prosthetic valve support 22 is implanted at anative semilunar valve of the subject (e.g., an aortic valve or apulmonary valve), clips 30 typically move toward each other duringventricular diastole, and away from each other during ventricularsystole.

Subsequently (e.g., immediately subsequently, or after more than aminute, e.g., after more than 2 minutes, e.g., after more than 5minutes, such as after more than an hour), a prosthetic valve 150 istransluminally delivered, in a compressed configuration thereof (e.g.,within a delivery tube 160), to the native valve, and implanted at thenative valve by coupling the prosthetic valve to prosthetic valvesupport 22. Implantation of prosthetic valve 150 replaces check valvefunctionality of the native valve with a substitute check valvefunctionality of the prosthetic valve. The substitute check valvefunctionality is provided by one or more prosthetic check valve elements(e.g., valve members, such as leaflets, a ball, or a disc), such asthose known in the art, which the prosthetic valve comprises (notshown).

Typically, and as shown in FIG. 3H, respective portions of prostheticvalve 150 are placed within opening 61 (defined by upstream supportportion 60) and/or opening 81 (defined by stabilizing element 80), andare expanded such that the respective portions engage the upstreamsupport portion and the stabilizing element, respectively. Typically,prosthetic valve 150 is configured to automatically expand upondeployment from delivery tube 160, and radially-expansive force appliedby prosthetic valve 150 to upstream support portion 60 and/orstabilizing element 80 facilitates coupling of the prosthetic valve toprosthetic valve support 22.

FIG. 3I shows prosthetic valve 150 having been fully deployed andcoupled to prosthetic valve support 22. That is, FIG. 3I shows animplant 180, comprising prosthetic valve support 22 and prosthetic valve150, having been implanted at native valve 120 (e.g., at mitral valve122). Prosthetic valve 150 is described in more detail hereinbelow.

Typically, diameter d3 of upstream support portion 60 is greater than adiameter d5 of the native valve (e.g., a diameter of the orifice of thenative valve, e.g., an inner diameter of the annulus of the nativevalve). Further typically, diameter d4 of opening 61 is smaller thandiameter d5. When prosthetic valve 150 is expanded within opening 61 ofthe upstream support portion, a diameter d6 of the prosthetic valve istypically restricted by the upstream support portion to the samediameter as diameter d4 of opening 61. For some applications, contactbetween prosthetic valve 150 and upstream support portion 60 (e.g.,resulting from the radially-expansive force of the valve on the support)couples the prosthetic valve to the prosthetic valve support, and/orinhibits retrograde leakage of blood therebetween.

When implanted at the native valve (e.g., when in respective expandedconfigurations), a height d9 of prosthetic valve 150 is typically atleast 1.5 times greater (e.g., at least 3 times greater, such as atleast 5 times greater) than the total height of upstream support portion60. Typically, height d9 is at least 1.5 times greater (e.g., at least 3times greater, such as at least 5 times greater) than depth d10 ofopening 61.

As described hereinabove, upstream support portion 60 is configured tobe placed against an upstream side of the native valve. It should benoted, that radial expansion of prosthetic valve 150 against innerperimeter 68 of upstream support portion 60, thereby typically does notcause the prosthetic valve support to apply a radially-expansive forceto the native valve annulus. For some applications of the invention,this expansion of prosthetic valve 150 does not cause the prostheticvalve support to apply the radially-expansive force to the native valveannulus because no part of the prosthetic valve support thatcircumscribes the prosthetic valve is sandwiched between the prostheticvalve and the native valve annulus.

For some applications, prosthetic valve 150 is couplable to upstreamsupport portion 60 at a plurality of positions along the length of theprosthetic valve. That is, a physician can couple the prosthetic valveat a plurality of depths within the support. For some applications, theprosthetic valve is couplable to the upstream support portion at acontinuum of positions along the length of the prosthetic valve. Thatis, a physician can couple the prosthetic valve to the support at acontinuum of depths within the support. For example, in someapplications in which the prosthetic valve is configured to be coupledto the upstream support portion solely by the radially-expansive force,the prosthetic valve may be coupled to the upstream support portion at acontinuum of positions along the length of the prosthetic valve.

For some applications, sealing between implant 180 and native valve 120is facilitated by native leaflets 128 being pushed closed against theouter surface of the frame of the valve during systole, in a mannersimilar to that in which native valve leaflets of a healthy native valvecoapt during systole.

For applications in which diameters d4 and d6 are relatively large, theproportion (e.g., the surface area) of the native leaflets that ispushed against the outer surface of the valve during systole isrelatively large, thereby enhancing the sealing of the native leafletswith respect to the frame of the prosthetic valve. However, for someapplications, beyond a given size, as diameters d4 and d6 increase, thenative valve leaflets are pushed apart at the commissures, therebypotentially increasing a likelihood of paravalvular retrograde leakageof blood at the commissures. Therefore, for some applications of thepresent invention, prosthetic valve support 22 (and, typically,prosthetic valve 150) are selected such that diameters d4 and d6 areless than 90% (e.g., 5 less than 80%, e.g., less than 60%, such as lessthan 50%) of diameter d5 of the native valve (e.g., of the orifice ofthe native valve). Thus prosthetic valve support 22 facilitates sealingof the prosthetic valve with respect to the native valve, byfacilitating closing of the native valve leaflets around the outersurface of the prosthetic valve.

In experiments conducted by the inventors, a prosthetic valve support 22was implanted in two pigs. Both animals remained alive and stable (e.g.,were hemodynamically stable, and had stable breathing rate and oxygensaturation) for a duration of sufficient length to withdraw deliveryapparatus 140, introduce a valve-delivery system, and deploy (e.g.,implant) a prosthetic valve in opening 61 of the support. The periodbetween implanting prosthetic valve support 22 and implanting theprosthetic valve was between 5 and 10 minutes. During this duration, thenative valve of the animals functioned generally normally. For example,native leaflet movement and coaptation, and blood flow therebetween wasgenerally normal during this duration.

It is thereby hypothesized that, following implantation of prostheticvalve support 22, the heart of the subject is able to continue pumpingblood sufficiently to support the subject (e.g., to maintain hemodynamicstability) for longer than a minute, e.g., longer than 2 minutes, e.g.,longer than 5 minutes, such as longer than an hour. It is therebyhypothesized that a period of generally normal physiological activity ofthe subject of up to a minute, e.g., up to 2 minutes, e.g., up to 5minutes, such as up to an hour, between implantation of prosthetic valvesupport 22 and implantation of a prosthetic valve (e.g., prostheticvalve 150) is supported by prosthetic valve support 22. It is therebyhypothesized that, for some applications, the implantation of implant180 may be performed without the use of cardiopulmonary bypass. It isthereby further hypothesized that replacement of a native valve withimplant 180, may, for some applications, be performed in a human,“off-pump,” as was performed in the pig experiments.

Reference is again made to FIG. 3I. For some applications of theinvention, the prosthetic valve that is expanded within, and coupled to,prosthetic valve support 22, comprises a generally cylindricalprosthetic valve. For some applications, the prosthetic valve comprisesa prior art prosthetic valve, e.g., a currently commercially-availableprosthetic valve. That is, for some applications, prosthetic valvesupport 22 may be used to facilitate implantation of a prior artprosthetic valve, such as a currently commercially-available prostheticvalve. For some applications, and as shown in FIG. 3I, the prostheticvalve comprises prosthetic valve 150, which comprises (1) a generallycylindrical valve body 152 (e.g., a primary structural element), withinwhich one or more prosthetic check valve elements (e.g., valve members,such as leaflets, a ball, or a disc) are disposed (not shown), and (2)one or more valve-anchoring elements 154 which protrude (e.g., radially)from the valve body. Typically, valve-anchoring elements 154 aredisposed at a downstream end of prosthetic valve 150 (e.g., at adownstream end of valve body 152), and protrude outward and upstream.For some applications, and as shown in FIG. 3I, valve-anchoring elements154 fold back toward valve body 152, and are configured to sandwichstabilizing element 80, clips 30 and/or native leaflets 128 between thevalve-anchoring elements and the valve body. For some applications,prosthetic valve 150 does not comprise valve-anchoring elements 154.

As described hereinabove, coupling of prosthetic valve 150 to prostheticvalve support 22 is typically facilitated by radially-expansive forceapplied by the valve to the support. Typically, prosthetic valve 150comprises an expandable lattice-structure frame 151 (e.g., comprising aplurality of struts). For applications of the invention in whichupstream support portion 60 comprises inwardly-protruding barbs 67(e.g., as shown in FIGS. 1A and 2A), the barbs protrude into frame 151(e.g., between struts thereof), thereby further facilitating coupling ofthe prosthetic valve to the prosthetic valve support.

Typically, at least portions of the inner surface of prosthetic valve150 (e.g., of valve body 152) are covered with a covering 156, tofacilitate channeling of blood through the valve body, as is known inthe art. That is, at least portions of prosthetic valve 150 (e.g., ofvalve body 152) are lined with covering 156. Covering 156 may comprisethe same material(s) as covering 64 described hereinabove, and/or maycomprise other materials.

For some applications, an upstream portion of prosthetic valve 150(e.g., of valve body 152) alternatively or additionally comprises anetting 158, which facilitates coupling of the prosthetic valve toprosthetic valve support 22. Netting 158 may be disposed on the innersurface and/or the outer surface of the upstream portion of theprosthetic valve (e.g., of valve body 152), and/or between the struts offrame 151. Typically, netting 158 is disposed upstream of a point atwhich leaflets 182 contact (e.g., seal around) valve body 152.

Typically, netting 158 facilitates coupling of prosthetic valve 150 toprosthetic valve support 22 by providing a higher-resolution latticethrough which barbs 67 of the prosthetic valve support are configured toprotrude. Netting 158 may additionally insulate respective metallicsurfaces of the prosthetic valve and the prosthetic valve support (e.g.,of frames 62 and 151) from each other. It is hypothesized that thisinsulation reduces fatigue, corrosion, chipping and/or wear of themetallic surfaces, and/or electrostatic discharge between the metallicsurfaces.

For some applications, a material that inhibits (e.g., prevents) tissuegrowth (e.g., polytetrafluoroethylene (PTFE), and/or pericardium) may bedisposed on a surface of prosthetic valve 150 and/or prosthetic valvesupport 22 (e.g., clips 30 thereof). Alternatively or additionally, amaterial that facilitates (e.g., enhances) tissue growth (such aspolyethylene terephthalate; PET) may be disposed on a surface of theprosthetic valve and/or the prosthetic valve support (e.g., clips 30thereof), in order to facilitate sealing and/or coupling to the nativevalve.

It is hypothesized that the use of prosthetic valve support 22advantageously facilitates delivery of a prosthetic valve via a catheternarrower than 28 Fr (i.e., less than 9.3 mm), e.g., narrower than 24 Fr(i.e., less than 8 mm), such as by allowing the use of a “minimalistic”prosthetic valve, comprising a generally cylindrical valve body, andvalve members (e.g., leaflets) disposed therein, and comprising few orno other components and/or appendages. Typically, prosthetic valvesupport 22 is also delivered via a similarly narrow catheter, e.g., viathe same catheter. The use of such a narrow catheter advantageouslyfacilitates transluminal (e.g., transfemoral) delivery and implantationof the prosthetic valve and prosthetic valve support.

It is to be noted that, although FIGS. 3A-I show prosthetic valvesupport 22 being implanted and used to facilitate implantation of aprosthetic valve, the techniques described may be applied to otherprosthetic valve supports described herein (e.g., prosthetic valvesupports 220, 322, 422 and 522), mutatis mutandis.

Reference is made to FIGS. 4A-F, which are schematic illustrations of asystem 200 for facilitating controlled expansion and/or retrievabilityof upstream support portion 60, in accordance with some applications ofthe invention. System 200 comprises one or more holding members 134,reversibly coupled to upstream support portion 60 by one or morecoupling leads 202 (e.g., coupling wires). Typically, two or more (e.g.,three) holding members are coupled to the upstream support portion viatwo or more (e.g., three) coupling leads. Typically, the ends of eachcoupling lead 202 are disposed within holding members 134, or moreproximally (e.g., outside a body of the subject). Coupling leads 202 maycomprise metallic wire, suture, or any other suitable material.

A portion (e.g., a middle portion) of each coupling lead 202 is disposedwithin (e.g., threaded and/or looped through) a respective portion ofupstream support portion 60, thereby coupling the upstream supportportion to holding members 134. Typically, this middle portion of eachcoupling lead is disposed through a peripheral region (e.g., close to anouter edge 69) of the prosthetic valve support.

For example, and as shown in FIG. 4A, three coupling leads 202 (e.g.,coupling leads 202 a, 202 b, and 202 c) couple three respective holdingmembers 134 (e.g., holding members 134 a, 134 b and 134 c) to upstreamsupport portion 60. One end of each coupling lead 202 extends from arespective holding member 134, passes around (e.g., is looped and/orthreaded through) upstream support portion 60, and returns to the sameholding member. Thereby, each coupling lead is configured to apply arespective annular pulling force to the entire upstream support portion,when the coupling lead is pulled.

For some applications of the invention, system 200 is configured tofacilitate transluminal retrieval of upstream support portion 60following expansion of the upstream support portion at the native valve.Upstream support portion 60 is deployed at the native valve, e.g., asdescribed with reference to FIGS. 3C-F, mutatis mutandis. Should it bedesirable and/or necessary to retrieve upstream support portion 60 intodelivery tube 130, and/or to remove the upstream support portionentirely from the subject, pulling of coupling leads 202 recompressesupstream support portion 60 into a generally cylindrical configuration,e.g., toward and/or into the compressed delivery configuration thereof(FIGS. 4B-D). Subsequently, upstream support portion 60 may be withdrawninto delivery tube 130 (FIGS. 4E-F).

System 200 may alternatively or additionally be configured to facilitatecontrolled expansion of upstream support portion 60. During deploymentof upstream support portion 60, coupling leads 202 are graduallyreleased (e.g., fed distally). This technique may be understood byconsidering FIGS. 4B-F in reverse order, mutatis mutandis. Thereby, therate of expansion of upstream support portion 60 is controllable.Alternative configurations and/or arrangements of coupling leads 202 maybe used, e.g., to facilitate controlled expansion of different portionsof upstream support portion 60.

It is to be noted that the techniques described with reference to FIGS.4A-F may be used in combination with other upstream support portionsdescribed herein (e.g., upstream support portions 90 and 100), mutatismutandis.

Reference is made to FIG. 5, which is a schematic illustration of a stepin the implantation of prosthetic valve support 22, in accordance withsome applications (e.g., alternative applications) of the invention. Forsome applications, the step shown in FIG. 5 is performed after theimplantation sequence steps shown in FIGS. 3A-3D, and prior to the stepsshown in FIGS. 3F-3I, e.g., instead of or in addition to the step shownin FIG. 3E, mutatis mutandis. FIG. 5 shows prosthetic valve supportsubsequent to the coupling of clips 30 to leaflets 128 of the nativevalve, and prior to the complete release (e.g., the complete expansion)of upstream support portion 60.

For some applications of the invention, it may be desirable and/ornecessary to hold clips 30 closer together than they would otherwise bedisposed following complete release, and thereby expansion, of upstreamsupport portion 60. FIG. 5 shows clips 30 being held closer together, byholding of portions of upstream support portion 60 that are in thevicinity of clips 30, closer together. At least one coupling lead (e.g.,coupling wire) 210 is coupled to these portions of upstream supportportion 60, and holds the portions together, as shown in FIG. 5.Coupling lead 210 may comprise metallic wire, suture, or any othersuitable material.

At a later time (e.g., closer to a time at which prosthetic valve 150 isto be implanted, such as at the time at which the prosthetic valve isimplanted), coupling lead 210 is released, such that the upstreamsupport portion (and the prosthetic valve support as a whole) movestoward the configuration shown in FIG. 3F and/or 3G.

For example, and as shown in FIG. 5, two or more coupling leads 210 mayextend through a holding member 212, and loop through respectiveportions of upstream support portion 60. The coupling leads aredecoupled from the skirt by releasing one end of each coupling lead, andunlooping the coupling lead from the upstream support portion. For someapplications, holding member 212 comprises holding member 134, e.g., asdescribed with reference to FIGS. 3C-F.

It is to be noted that the techniques described with reference to FIG. 5may be combined with other techniques and apparatus described herein.For example, the techniques described with reference to FIG. 5 may beused for implanting other prosthetic valve supports described herein,mutatis mutandis.

Reference is made to FIGS. 6A-B, which are schematic illustrations of aprosthetic valve support 522, comprising tissue-engaging elements 24that are couplable to each other, and decouplable from each other (e.g.,reversibly coupled to each other), in accordance with some applicationsof the invention. Prosthetic valve support 522 typically furthercomprises upstream support portion 60 and/or stabilizing element 80, andthe tissue-engaging elements of the prosthetic valve support typicallycomprise clips 30. For some applications, prosthetic valve support 522comprises prosthetic valve support 22 (e.g., as described with referenceto FIGS. 1A-D), and/or may be used in combination with techniquesdescribed herein (e.g., with reference to FIGS. 3A-I and/or 8), mutatismutandis. For some applications, prosthetic valve support 522 does notcomprise stabilizing element 80 (e.g., as described for prosthetic valvesupport 322 with reference to FIG. 2C, mutatis mutandis), and/or doesnot comprise upstream support portion 60 (e.g., as described forprosthetic valve support 422 with reference to FIG. 2D, mutatismutandis). Similarly, the tissue-engaging elements of other prostheticvalve supports described herein may be reversibly coupled to each otheras described for the tissue-engaging elements of prosthetic valvesupport 522, mutatis mutandis. Typically, prosthetic valve support 522is provided with tissue-engaging elements 24 fixedly coupled to eachother, and configured to be transluminally, intracorporeally decoupledfrom each other. Alternatively or additionally, tissue-engaging elements24 may be configured to be extracorporeally and/or intracorporeally(e.g., transluminally) couplable to each other by a physician.

FIGS. 6A-B show prosthetic valve support 522 following implantationthereof at the native valve (e.g., as shown in FIGS. 3A-F, mutatismutandis), and before coupling of a prosthetic valve to the prostheticvalve support (e.g., as shown in FIGS. 3H-I, mutatis mutandis), e.g.,instead of or in addition to the step shown in FIG. 3G, mutatismutandis. For some applications, FIG. 6A is thereby comparable to FIG.3G, mutatis mutandis.

FIG. 6B shows a view from upstream of mitral valve 122 (e.g., from leftatrium 124), showing the valve (e.g., leaflets 128) moving (e.g.,beating) between open and closed states thereof. As is known in the art,each leaflet 128 of mitral valve 122 is generally defined as beingdivided into three scallops: scallops A1, A2 and A3 of the anteriorleaflet, and scallops P1, P2 and P3 of the posterior leaflet.Tissue-engaging elements 24 are coupled to respective portions ofleaflets 128 (e.g., scallops A2 and P2 of the anterior and posteriorleaflets, respectively), and to each other, and thereby hold theportions of the leaflets to which they are coupled, close to each other(e.g., together). Portions of the leaflets that are not held close toeach other (e.g., at least portions of scallops P1, P3, A1 and A3) aretypically generally able to move (e.g., flap) in response to beating ofthe heart. Thereby, the implantation of prosthetic valve support 522shown in FIGS. 6A-B generates two orifices 530, each orifice defined by(e.g., surrounded by) a respective portion of each leaflet, and thereby,in effect, functioning as a respective check valve. For example, thenative valve may function as two (e.g., parallel) check valves. For someapplications of the invention, the resulting arrangement of leaflets 128resembles the “double-orifice” arrangement of leaflets of a valve thathas been repaired using the Alfieri stitch, as is known in the mitralvalve repair art. Thereby, prosthetic valve support 522 is configured tobe coupled to the native heart valve (e.g., to leaflets thereof) withouteliminating check valve functionality of the native heart valve, bycoupling together respective portions of the two leaflets, such that (1)the native leaflets define two orifices, and (2) the native valvefunctions as two (e.g., parallel) check valves (e.g., in a manner thatis modified with respect to the natural function of the native valve).

Subsequently (e.g., immediately subsequently, or after more than aminute, e.g., after more than 2 minutes, e.g., after more than 5minutes, such as after more than an hour), a prosthetic valve istransluminally delivered, and implanted at the native valve by couplingthe prosthetic valve to prosthetic valve support 522 (e.g., as describedwith reference to FIGS. 3H-I, mutatis mutandis). Prior to (e.g.,immediately prior to) implantation of the prosthetic valve,tissue-engaging elements 24 are decoupled from each other, such that thetissue-engaging elements (and thereby leaflets 128) are movable awayfrom each other, and such that the prosthetic valve may be disposedtherebetween during coupling of the prosthetic valve to the prostheticvalve support. For some applications of the invention, between (1) thedecoupling of the tissue-engaging elements from each other, and (2) thecoupling of the prosthetic valve to the prosthetic valve support, theprosthetic valve support allows (1) the native valve (e.g., the leafletsthereof) to define a single orifice, and (2) the native valve tofunction as a single check valve (e.g., as described with reference toFIG. 3G, mutatis mutandis).

For some applications of the invention, tissue-engaging elements 24 arecoupled to each other by a locking element (e.g., a locking wire), andthe locking element is unlocked (e.g., the locking wire is cut orotherwise decoupled), prior to implantation of the prosthetic valvesupport. For some applications of the invention, tissue-engagingelements 24 are coupled to each other by a coupling lead that which isheld in place, and removed, decoupled, and/or loosened immediately priorto implantation of the prosthetic valve. For example, the coupling leadmay extend through a holding member and be looped through and/or aroundthe tissue-engaging elements. For some such applications, the holdingmember may comprise holding member 212, and the coupling lead maycomprise coupling lead 210 (e.g., described with reference to FIG. 5,mutatis mutandis), the coupling lead being coupled to tissue-engagingelements 24, rather than to portions of the upstream support portion.For some applications of the invention, prosthetic valve support 522 isconfigured such that the tissue-engaging elements are decoupled (e.g.,automatically) when the prosthetic valve is implanted at the nativevalve (e.g., when the prosthetic valve is expanded within the prostheticvalve support).

It is hypothesized that, following implantation of prosthetic valvesupport 522, the heart of the subject is able to continue pumping bloodsufficiently to support the subject and/or to maintain hemodynamicstability for longer than a minute, e.g., longer than 2 minutes, e.g.,longer than 5 minutes, such as longer than an hour. It is therebyhypothesized that a period of generally normal physiological activity ofthe subject of up to a minute (e.g., up to 2 minutes, e.g., up to 5minutes, such as up to an hour) between implantation of prosthetic valvesupport 522 and implantation of a prosthetic valve, is supported byprosthetic valve support 522. It is thereby hypothesized that theimplantation of an implant comprising prosthetic valve support 522 and aprosthetic valve, may be performed without the use of cardiopulmonarybypass. It is thereby hypothesized that replacement of a native valvewith such an implant may be performed in a human, “off-pump.”

It is to be noted that the techniques described with reference to FIGS.6A-B may be combined with other techniques and apparatus describedherein. For example, tissue-engaging elements (e.g., clips) of otherprosthetic valve supports described herein may be reversibly coupled toeach other, so as to achieve the double-orifice configuration of thenative valve described with reference to FIGS. 6A-B, mutatis mutandis.

Reference is made to FIG. 7, which is a schematic illustration of aprosthetic valve support 220, comprising upstream support portion 60 andthree clips 30 (or other tissue-engaging elements 24), in accordancewith some applications of the invention. Clips 30 are typically coupledto upstream support portion 60 via connectors 70, as describedhereinabove, mutatis mutandis. For some applications, and as shown inFIG. 7, prosthetic valve support 220 is configured to be coupled tomitral valve 122 of the subject. One clip 30 is configured to be coupledto anterior leaflet 128 a of the mitral valve (e.g., to the A2 scallopthereof), and two clips are configured to be coupled to posteriorleaflet 128 b (e.g., to the P1 and P3 scallops thereof, respectively).For some applications, prosthetic valve support 220 is configured to becoupled to a native tricuspid valve of the subject, and each clip 30 isconfigured to be coupled to a respective leaflet of the tricuspid valve.

It is to be noted that the techniques described with reference to FIG. 7may be combined with other techniques and apparatus described herein.For example, other prosthetic valve supports described herein (e.g.,prosthetic valve supports 220, 322, 422 and 522) may comprise threetissue-engaging elements, mutatis mutandis.

Reference is made to FIG. 8, which is a schematic illustration ofimplantation, in heart 250 of the subject, of a prosthetic valve 240,facilitated by prosthetic valve support 22, in accordance with someapplications of the invention. For some applications, prosthetic valve240 comprises and/or has features of prosthetic valve 150, describedhereinabove. For some applications, and as shown in FIG. 3H, both theprosthetic valve support and the prosthetic valve are configured to bedelivered from the upstream side of mitral valve 122, e.g.,transfemorally and/or transseptally. For some applications of theinvention, the prosthetic valve is configured to be delivered via aretrograde approach. For example, and as shown in FIG. 8, followingimplantation of prosthetic valve support 22 at mitral valve 122,prosthetic valve 240 is delivered via left ventricle 126, e.g., viaaorta 252 such as via the femoral artery of the subject. Alternatively,prosthetic valve 240 may be delivered transapically. For applications inwhich the prosthetic valve is delivered via a retrograde approach,prosthetic valve support 22 is typically delivered as describedhereinabove, but may alternatively be delivered via a retrogradeapproach.

It is to be noted that the techniques described with reference to FIG. 8may be combined with other techniques and apparatus described herein.For example, the techniques described with reference to FIG. 8 may beused for implanting other prosthetic valves described herein, and/or fordelivering a prosthetic valve to other prosthetic valve supportsdescribed herein, mutatis mutandis.

Reference is made to FIGS. 9A-C, which are schematic illustrations ofprosthetic valve supports, each comprising upstream support portion 60,coupled to tissue-engaging elements 24 (comprising clips 30) via one ormore variable-length connectors 260, in accordance with respectiveapplications of the invention. Variable-length connectors 260 aretypically positioned in the same or similar way as connectors 70, andtypically perform the same or similar functions as connectors 70,described hereinabove.

FIG. 9A shows a prosthetic valve support 270, comprising variable-lengthconnectors 260, embodied as adjustable-length connectors 272, inaccordance with some applications of the invention. Connectors 272comprise a holding wire 274, which is slidably coupled to upstreamsupport portion 60, is fixedly coupled to tissue-engaging elements 24,and defines a rack 276, comprising a plurality of teeth 277, disposedalong at least part of the length of the holding wire. The distancebetween upstream support portion 60 (e.g., inner perimeter 68 thereof)and each tissue-engaging element 24 is adjustable by adjusting thelength of the respective holding wire 274 that is disposed between theupstream support portion and the tissue-engaging element. Typically,this length is adjusted by pulling the holding wire proximally. Thereby,the length of connectors 272 is variable, by the connectors beingadjustable.

An engaging element 278 (e.g., a pawl, a ridge, or a tooth), typicallywithin a ratchet housing 280, allows the length of holding wire 274between the upstream support portion and the clip to be shortened, butnot to be lengthened. Thereby, holding wire 274 (e.g., rack 276 thereof)and ratchet housing 280 (e.g., engaging element 278 thereof) act as aratchet. For some applications, and as shown in FIG. 9A, ratchet housing280 is movable with respect to upstream support portion 60, and is sliddistally over holding wire 274, such as by a pusher 282 (e.g., acontroller tube). Alternatively, ratchet housing 280 is fixedly coupledto upstream support portion 60, e.g., such that the length of holdingwire 274 is adjusted by pulling the holding wire proximally. Typically,but not necessarily, the length of holding wire 274 (and thereby ofconnectors 272) is adjusted subsequent to coupling of clips 30 to thenative leaflets, and further typically, also subsequent to deployment ofupstream support portion 60.

FIG. 9B shows a prosthetic valve support 290, comprising variable-lengthconnectors 260, embodied as elastic connectors 292 (e.g., stretchableconnectors), in accordance with some applications of the invention.Connectors 292 comprise one or more (e.g., two) elastic elements 294,such as tension springs (e.g., coil tension springs). The distancebetween upstream support portion 60 (e.g., inner perimeter 68 thereof)and each clip is variable due to stretching and contracting of elasticelements 294. Thereby, the length of connectors 292 is variable, by theconnectors being elastic.

The length, elasticity and/or force constant of elastic elements 294 maybe adapted to the native valve to which prosthetic valve support 290 iscoupled, and/or to the individual subject (e.g., pre-selected accordingto the native valve and/or the individual subject). For example, elasticelements that have a relatively low force constant may allow leaflets ofthe native valve to move more freely, and elastic elements that have arelatively high force constant may couple the prosthetic valve supportto the native valve more fixedly. Alternatively or additionally,connectors 260 may be configured to stretch and contract with movement(e.g., flapping) of the leaflets of the native valve, may thereby allowthe leaflets to move more freely compared to some inelastic connectors,and may thereby facilitate the coupling of the prosthetic valve supportto the native valve without eliminating check valve functionality of thenative valve.

FIG. 9C shows a prosthetic valve support 300, comprising variable-lengthconnectors 260, embodied as elastic connectors 302, in accordance withsome applications of the invention. Connectors 302 comprise an elasticelement 304, such as a tension spring (e.g., a coil tension spring). Forsome applications, elastic element 304 comprises elastic element 294,described with reference to FIG. 9B. Connectors 302 further comprise arestrictor 306, which restricts elasticity of element 304. Typically,restrictor 306 holds elastic element 304 in an expanded (e.g.,stretched) state. Typically, restrictor 306 is releasable (e.g.,decouplable) from elastic element 304, so as to allow the elasticelement to contract.

For some applications, restrictor 306 may be mechanically releasable(e.g., removable) by the user. For some applications, and as shown inFIG. 9C, restrictor 306 may comprise a material that disintegrates inthe body (e.g., a material that is at least in part soluble and/orbiodegradable and/or biosorbent). For such applications, restrictor 306typically disintegrates over a predictable period of time e.g., between15 minutes and 1 week, such as between 30 minutes and 3 days, forexample, between 1 hour and 1 day. For some applications, restrictor 306is configured to decouple from (i.e., release) elastic element 304gradually, e.g., in stages. For some applications, restrictor 306 iscoupled to elastic element 304 and/or another part of prosthetic valvesupport 300, such that, following the release of the elastic element,the restrictor is retained, so as not to enter the vasculature of thesubject.

For some applications of the invention, prosthetic valve support 300 andconnectors 302 are used in instances in which it is desirable to have afirst period during which the connectors are longer (e.g., prior toimplantation of a prosthetic valve), and a second period during whichthe connectors are shorter (e.g., subsequent to implantation of theprosthetic valve).

Reference is again made to FIGS. 9A-C. It should be noted thatthroughout this patent application, including in the claims, the term“variable”, with respect to the length of the connectors that coupletissue-engaging elements 24 (e.g., clips 30) to upstream support portion60, includes (1) length variability due to intervention, such as aphysician adjusting the length (e.g., as described for adjustable-lengthconnectors 272), and (2) length variability due to elasticity and/oranother configuration that facilitates the connector changing length,such as without intervention (e.g., as described for elastic connectors292 and 302). It is hypothesized that, for some applications, connectorlength variability (1) facilitates reduction of valve regurgitationprior to implantation of the prosthetic valve (2) provides adjustabilityfor anatomical differences (e.g., leaflet size) between subjects, and/or(3) increases stability of the prosthetic valve, e.g., by reducing axialrotation of the prosthetic valve, such as by the connector length beingshortened after implantation of the prosthetic valve.

It is to be noted that the apparatus and techniques described withreference to FIGS. 9A-C may be combined with other techniques andapparatus described herein. For example, any of the prosthetic valvesupports may comprise variable-length connectors 260 (e.g.,adjustable-length connectors 272, elastic connectors 292, and/or elasticconnectors 302), mutatis mutandis. Similarly, connector lengthadjustment may be used in combination with the implantation techniquesdescribed with reference to FIGS. 3A-I and/or 8, mutatis mutandis.

Reference is again made to FIGS. 1A-9C. For some applications of theinvention, one or more of the elements, portions and/or componentsdescribed hereinabove comprise radiopaque markers so as to facilitateimplantation thereof (e.g., by using imaging techniques such asfluoroscopy). For example, tissue-engaging elements 24 (e.g., clips 30)and/or stabilizing element 80 may comprise radiopaque markers, e.g., soas to facilitate positioning (e.g., orientation) of the prosthetic valvesupport with respect to the native valve. Alternatively or additionally,inner perimeter 68 of upstream support portion 60 and/or stabilizingelement 80 may comprise radiopaque markers, e.g., so as to indicate theopening(s) in which the prosthetic valve is to be implanted.Alternatively or additionally, the prosthetic valve may compriseradiopaque markers to facilitate positioning thereof with respect to theprosthetic valve support.

Reference is again made to FIGS. 1A-9C. For some applications of theinvention, the tissue-engaging elements of the prosthetic valve supportsdescribed hereinabove are movable with respect to each other at at leastsome time subsequent to the coupling of the tissue-engaging elementsbeing coupled to the leaflets of the native valve. For example,tissue-engaging elements 24 (e.g., clips 30) of prosthetic valve support22 are movable with respect to each other, e.g., as shown in FIG. 3G.Similarly, tissue-engaging elements 24 (e.g., clips 30) of prostheticvalve support 522 are movable with respect to each other once they havebeen decoupled from each other.

Reference is again made to FIGS. 1A-9C. The prosthetic valve supportsdescribed hereinabove are typically configured to be coupled to theleaflets of the native valve without eliminating check-valvefunctionality of the native valve. That is, although the coupling of theprosthetic valve support to the native valve may alter the positionand/or movement of the native leaflets, the native valve stillfacilitates at least some net one-way movement of blood therethrough(e.g., as described with reference to FIGS. 3G and 6A-B). For some suchinstances, the altered position and/or movement of the native leafletsmay, in fact, enhance check valve functionality of the native valve,thereby substantially “repairing” the native valve. For some suchinstances, a physician may choose not to implant a prosthetic valveduring the same procedure as the implantation of the prosthetic valvesupport, but instead may choose to allow the subject to return toactivities of daily living, whilst retaining the option to implant aprosthetic valve at a later date. That is, for some applications of theinvention, the prosthetic valve support is configured to be implantedwithout a prosthetic valve, and to provide (1) repair of the nativevalve, and (2) an implantation site that is pre-prepared for subsequentimplantation of a prosthetic valve at a later date, should suchimplantation be subsequently considered necessary.

It is to be noted that, although some techniques described hereinaboveare generally illustrated as being used at the mitral valve of thesubject, the scope of the invention includes implanting a prostheticvalve support and prosthetic valve (e.g., those described hereinabove)at other native heart valves of the subject, such as at the tricuspidvalve, the aortic valve, or the pulmonary valve of the subject, mutatismutandis.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1-40. (canceled)
 41. Apparatus for use with a valve of a heart of asubject, the apparatus comprising: a delivery tool, transluminallyadvanceable to the heart, and comprising a clip controller; and animplant, having a central longitudinal axis, and coupled to a distalportion of the delivery tool, and comprising: a clip: disposed laterallyfrom the longitudinal axis, comprising a first arm, and a second armarticulatably coupled to the first arm, and configured to be attached toa leaflet of the valve by sandwiching the leaflet between the first armand the second arm by articulation between the first arm and the secondarm, such that the second arm is disposed laterally from the first arm;and a clip-controller interface, reversibly coupled to the clipcontroller, and comprising: a first interface portion, configured to beslid linearly by the clip controller, and a second interface portion,articulatably coupled to the first interface portion, and articulatablycoupled to the second arm, such that linear sliding of the firstinterface portion causes the second interface portion to (i) articulatewith respect to the first interface portion, and (ii) push the secondarm to articulate toward the central longitudinal axis.
 42. Theapparatus according to claim 41, wherein: the clip is a first clip, theleaflet is a first leaflet of the valve, and the first clip isconfigured to be attached to a middle scallop of the first leaflet; andthe implant further comprises a second clip, disposed on an oppositelateral side of the longitudinal axis from the first clip, andconfigured to be attached to a middle scallop of a second leaflet of thevalve such that, while the first clip is attached to the middle scallopof the first leaflet and the second clip is attached to the middlescallop of the second leaflet, the implant arranges the first leafletand the second leaflet into a double-orifice configuration.
 43. Theapparatus according to claim 42, wherein the first clip and the secondclip are controllable independently of each other.
 44. The apparatusaccording to claim 41, wherein the first arm comprises teeth, configuredto pierce the leaflet.
 45. The apparatus according to claim 44, whereinthe clip comprises padding, configured to cushion contact between theclip and the leaflet.
 46. The apparatus according to claim 41, whereinthe second interface portion is articulatably coupled to the second armat a lateral surface of the second arm.
 47. The apparatus according toclaim 41, wherein the implant comprises a locking element, configured tofacilitate locking of the clip subsequent to closing of the clip. 48.The apparatus according to claim 41, wherein the second arm isarticulatable by 60-180 degrees with respect to the first arm.
 49. Theapparatus according to claim 41, wherein the second arm is articulatableby 80-180 degrees with respect to the first arm.
 50. The apparatusaccording to claim 41, wherein the second arm is articulatable by100-180 degrees with respect to the first arm.
 51. The apparatusaccording to claim 41, wherein the second arm is articulatable by120-180 degrees with respect to the first arm.